EXTRACELLULAR VESICLES FROM PLASMA OF HIV-1-INFECTED INDIVIDUALS TRIGGER MACROPHAGE-MEDIATED INFLAMMATION AND HIF-1Α ACTIVITY

PEREZ, PAULA S.; DUETTE, GABRIEL; GERBER, PEHUÉN PEREYRA; RUBIONE, JULIA; ADAMCZYK, ALAN; ROMANIUK, ALBERTINA; SUED, OMAR; OSTROWSKI, MATIAS

Mar del Plata

Congreso; LXIV Reunión anual de la Sociedad Argentina de Inmunología; 2018

Sociedad Argentina de Inmunología

Chronic immune activation and inflammation are hallmarks ofHIV-1 infection and a major cause of serious non-AIDS events inHIV-1-infected individuals on antiretroviral treatment (ART), such asnon-AIDS malignancies, cardiovascular events, renal and hepaticdisease, bone disorders and neurocognitive impairment. Activatedmacrophages are responsible for sustaining chronic inflammationand therefore are key players in the pathogenesis of these diseases. The Hypoxia-Inducible Factor-1α (HIF-1α) is a transcriptionalactivator factor that plays a central role in cellular metabolism andfunction, including the pro-inflammatory activity of macrophages.Extracellular vesicles (EVs) comprise a heterogeneous group ofmembrane-surrounded structures secreted by a wide variety of cellswhich mediate intercellular communication. The aim of this workwas to evaluate the role of circulating EVs from HIV-1-infected individuals in the activation of macrophages and the role of HIF-1αin this process.EVs from 2 ml of plasma from HIV-1-negative and ART-treatedHIV-1-positive individuals with undetectable viral load were isolated by size exclusion chromatography followed by centrifugation.Plasma-derived EVs were incubated with monocyte-derived macrophages for 24 h and the production of pro-inflammatory cytokinesin cell culture supernatants was evaluated by enzyme immunoassayand/or cytokine bead array. The ability of EVs to trigger HIF-1α activity was studied in the reporter cell line HeLa HRE-GFP.Macrophages treated with EVs from HIV-1-infected individuals produced significantly higher levels of IL-6 (p